Study to Evaluate is ECV Success is Improved and the Side Effects Reduced With the Use of IV NTGL Versus Terbutaline

Intravenous Terbutaline Versus Intravenous Nitroglycerine for External Cephalic Version: A Double-Blinded Randomized Controlled Trial in Nulliparous Women

Breech presentation of a term pregnancy is a common occurrence. A procedure known as external cephalic version (ECV) is frequently used by obstetricians to turn the baby into the vertex position prior to delivery in order to avoid a cesarean section and the associated risks. Medications to relax the uterus, known as tocolytics, are used in conjunction with the procedure as they have been shown to improve the success rate of ECV, but with inconsistent, varying results.

Study Overview

• Status: Terminated
• Conditions: External Cephalic Version
• Intervention / Treatment: Drug: Intravenous Terbutaline; Drug: Intravenous Nitroglycerine

Detailed Description

Breech presentation occurs in approximately 3-4% of all births and all women with breech presentation at term undergo cesarean delivery. The only way to avoid a cesarean is to manually turn the baby prior to the date of delivery, a procedure known as elective external cephalic version (ECV). ECV has been shown to reduce the frequency of breech presentation at term and thus lessen the risks associated with breech delivery and those of cesarean section, with little risk to the mother or baby. Tocolysis, administered immediately prior to the ECV and commonly used at The Mount Sinai Hospital, has been shown to improve the success rate of ECV. Several different agents are known to cause tocolysis. These include beta-mimetics (ritodrine, terbutaline), nitroglycerine (NTGL) and nifedipine.Terbutaline has been shown to improve success rate of ECV. Another study published in 2004 by El-Sayed et al showed that subcutaneous terbutaline was associated with higher rates of successful ECV than IV NTGL in term patients. There is inconsistent data in regard to the success rate of ECV with NTGL. In a study published in 2003 by Bujold et al, NTGL was associated with a higher rate of side effects and a lower rate of successful ECV when compared to ritodrine. Another study published in 2009 by Hilton et al showed that NTGL was more efficacious for ECV in nulliparous versus multiparous women. Yet another study published in 2009 by Yanny et al showed no differences between sublingual NTGL versus placebo in efficacy, and reported no significant side effects. A study published in 2003 by Bujold et al showed that sublingual NTGL was associated with a higher incidence of headache and did not improve the success rate of ECV. It may be beneficial to use NTGL instead of terbutaline because NTGL is a shorter acting agent and the procedure itself only lasts 10-15 minutes. Additionally, both medications have side effects. Terbutaline is associated with maternal tachycardia, hyperglycemia, hypokalemia, pulmonary edema, cardiac arrhythmias, hypertension and myocardial ischemia, and NTGL is associated with maternal nausea, vomiting, headache, and hypotension. For both medications the side effects are self- limiting but depending on the patient's co-morbidities one drug may be beneficial for that individual patient.

To date no study has compared the efficacy of intravenous terbutaline versus intravenous NTGL in women presenting for ECV. The purpose of this study is to determine if the success rate of ECV can be improved with the use of IV NTGL.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female
• Between 18-35 years of age
• 37 weeks gestation
• Breech presentation

Exclusion Criteria:

• Patients with ruptured membranes
• Multiple gestation
• Maternal age (age > 35)
• With known medical comorbidities (including hypertension (HTN), arrhythmias, endocrinologic diseases such as diabetes and thyroid disease, scoliosis, asthma)
• Allergies to nitroglycerine or terbutaline
• Prior abdominal or uterine surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Intravenous Terbutaline; 0.25 mL of Intravenous Terbutaline	Drug: Intravenous Terbutaline; 0.25 mL of Intravenous Terbutaline. This will be followed 3 minutes later by an injection of 0.25 mL IV of normal saline.; Other Names: Terbutaline; Brethine; Bricanyl; Brethaire; Terbutalin; (RS)-5-[2-(tert-butylamino)-1-hydroxyethyl]benzene-1,3-diol)
ACTIVE_COMPARATOR: Intravenous Nitroglycerine; IV nitroglycerine 100 micrograms three minutes before beginning the procedure, then followed by a second dose 3 minutes later just after the start of the procedure for a total of 200 micrograms.	Drug: Intravenous Nitroglycerine; The dose of IV nitroglycerine will be 100 micrograms three minutes before beginning the procedure, and because of it's short half-life (approximately 3 minutes) will be followed by a second dose 3 minutes later just after the start of the procedure for a total of 200 micrograms.; Other Names: Nitroglycerine; Nitroglycerin; Trinitroglycerin; Trinitroglycerine; nitro; 1,2,3-trinitroxypropane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful Version of the Fetus Into the Vertex Position	Number of participants that had successful version of the fetus into the vertex position.	average of 1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypotension	Number of participants with hypotension	average of 1 hour
Need for Cesarean Delivery	Number of participants that needed a cesarean delivery	average of 1 hour
Tachycardia	Number of participants that had tachycardia	average of 1 hour

Collaborators and Investigators

• Sponsor: Yaakov Beilin

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (ACTUAL): April 1, 2015
• Study Completion (ACTUAL): April 1, 2015

Study Registration Dates

• First Submitted: April 13, 2014
• First Submitted That Met QC Criteria: April 13, 2014
• First Posted (ESTIMATE): April 16, 2014

Study Record Updates

• Last Update Posted (ACTUAL): June 14, 2017
• Last Update Submitted That Met QC Criteria: May 14, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: breech; External Cephalic Version
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Sympathomimetics; Nitroglycerin; Terbutaline
• Other Study ID Numbers: GCO 14-0636